The central aim of the proposal is to identify and characterize host cell regulatory factors that govern productive infections in vitro by animal riboviruses and elucidate the underlying mechanisms. (A) Studies with the negative-stranded bovine rhabdovirus vesicular stomatitis virus (VSV) will utilize the following approaches: 1. Newly isolated host-restricted (hr) mutants will be comparatively studied for their biosynthetic defects and ability to complement other hr mutants or defined temperature-sensitive (ts) mutants of VSV in nonpermissive cells. Viral gene assignment for specific hr mutations is the objective of these experiments. 2. The working hypothesis will be tested that permissive cells contain intrinsic regulatory factors which are essential for transcription and replication of VSV RNA species. Depletion experiments will be conducted to implicate the existence of putative regulatory proteins which, if found, will be isolated and characterized for their biochemical and biological properties. Our goal is to determine the number and nature of obligatory host cell factors that control biogenesis of VSV. 3. The potentiation of VSV infections by DNA poxviruses in cells normally restrictive for wild-type virus or hr mutants will be studied to understand what essential host functions are supplanted by the helper virus. The ability of defined ts mutants, drug-inhibited virus or subviral components to potentiate VSV infections will be tested with an interest in possible enzymatic functions provided or induction of host-specific functions. The positive-stranded avian coronavirus infectious bronchitis virus (IBV) will be studied to characterize host transcription factors and nuclear functions required for productive infections. The effect of blocked host functions on viral biosynthesis will be examined.